Sv2c, a member of the synaptic vesicle glycoprotein 2 (SV2) family, is homologous to Sv2A and Sv2B. It is an N-glycosylated protein concentrated on small synaptic vesicles [2]. Sv2c is involved in vesicle trafficking, exocytosis, and neurotransmission, especially regulating dopamine release, and is known to be a receptor for botulinum neurotoxin/A (BoNT/A) [3]. It has a restricted expression pattern, mainly in phylogenetically old brain regions like the pallidum, substantia nigra, midbrain, brainstem, and olfactory bulb [2].

Genetic deletion of Sv2C in mice leads to reduced dopamine release in the dorsal striatum, reduced striatal dopamine content, disrupted α-synuclein expression, motor function deficits, and altered neurochemical effects of nicotine. Also, Sv2C expression is dramatically altered in postmortem brain tissue from Parkinson's disease (PD) cases but not in other neurodegenerative diseases, and this disruption was paralleled in mice overexpressing mutated α-synuclein, suggesting Sv2C disruption contributes to dopaminergic dysfunction in PD [4]. Additionally, in a mouse model of long-term dietary fiber deficiency, a deficit of Sv2C was found in the hippocampus along with cognitive impairment [1].

In conclusion, Sv2c plays crucial roles in synaptic function, especially in dopamine-related processes. Gene-knockout mouse models have been instrumental in revealing its role in PD and cognitive impairment. Understanding Sv2c's function provides insights into the mechanisms of these diseases and may offer potential therapeutic targets.